Medical imaging is a well-established technique (in the field of equipments for medical applications), which allows analyzing a body-part of a patient in a substantially non-invasive manner. A specific medical imaging technique is based on the recording of an echo signal that results from the application of ultrasound waves to the body-part. This technique may advantageously be implemented with the administration of an ultrasound contrast agent (UCA) to the patient (for example, consisting of a suspension of phospholipid-stabilized gas-filled microbubbles); as the contrast agent acts as an efficient ultrasound reflector, it enhances the visualization of a vascular system within the body-part where it is present.
Contrast agents, adapted to reach a specific (biological) target and then remain immobilized thereon, have also been proposed in the last years for facilitating the detection of specific pathologies. Particularly, these contrast agents are capable of attaching to selected tissues or receptors by means of a specific interaction therewith; for example, the desired behavior may be achieved by incorporating a targeting ligand in the formulation of the contrast agent (e.g., capable of interacting with tumoral tissues). In addition, contrast agents may also be conveyed or accumulated to a specific location, such as tissues or organs, by means of a non-specific interaction therewith; for example, the contrast agent may be recognized as a foreign substance by the immune system of the patient and then moved to the liver for its metabolism and elimination. In any case, once the contrast agent (either with specific or non-specific interaction) has reached the target remaining immobilized thereon, its detection may allow distinguishing pathologies that would be otherwise difficult to identify.
A possible problem associated with the detection of the immobilized contrast agent is that only a relatively small fraction of the total amount of the administered contrast agent actually reaches the target; conversely, most of the contrast agent continues to circulate (for example, until it is filtered out by the lungs and/or in the liver of the patient). The echo signal that is measured is then the result of different contributions, which are due to the immobilized contrast agent, to the circulating (free-flowing) contrast agent and to the surrounding tissues. Therefore, it may be quite difficult to distinguish the echo signal generated by the immobilized contrast agent from the one generated by the circulating contrast agent and the tissues; particularly, it may be almost impossible to differentiate the low concentration of immobilized contrast agent (often consisting of single particles thereof that reach the target individually) from the higher concentration of circulating contrast agent. This adversely affects the spatial delineation and the quantification of the immobilized contrast agent, thereby hindering the correct detection of the pathologies of interest.
Attempts have been made to improve the discrimination of the immobilized contrast agent. For example, “P. A. Dayton, D. Pearson, J. Clark, S. Simon, P. Schumann, R. Zutshi, T. Matsunaga, K. W. Ferrara, Ultrasonic Enhancement of  Expressing-Cells With Targeted Contrast Agents, 2003 IEEE Ultrasonics Symposium”, which is incorporated by reference proposes a solution that is based on the observation that the echo signal corresponding to the immobilized contrast agent has a bandwidth that is narrower than the one of the circulating contrast agent. This document then mentions the possibility of discriminating the different contributions in the echo signal exploiting the larger bandwidth that is observed for the circulating contrast agent.
However, no solution is available in the art for detecting the immobilized contrast agent with an acceptable degree of accuracy. Particularly, the problem of efficiently discriminating the immobilized contrast agent from the circulating contrast agent is still unresolved. In this context, it would also be desirable to quantify the concentration of the immobilized contrast agent at each location.
Therefore, nowadays it may be necessary to wait until the circulating contrast agent has completely disappeared before being able to identify the immobilized contrast agent; however, this requires a relatively long time (up to tens of minutes).
All of the above hinders the clinical application of currently available contrast-specific imaging techniques for the detection of immobilized contrast agents.